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Drugs in Context 2022Pediculosis capitis is a common human parasitic infestation in childhood. This article aims to provide a narrative updated review on the management of pediculosis... (Review)
Review
BACKGROUND
Pediculosis capitis is a common human parasitic infestation in childhood. This article aims to provide a narrative updated review on the management of pediculosis capitis.
METHODS
A PubMed search was performed with Clinical Queries using the key terms "pediculosis capitis" OR "head lice" OR "head louse". The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies and reviews published within the past 10 years. The search was restricted to articles published in English literature. The information retrieved from the search was used in the compilation of the present article.
RESULTS
Topical permethrin and pyrethrin formulated with piperonyl butoxide are the pediculicides of choice in areas where resistance to these products is low. When resistance to these products is suspected based on local levels of resistance or when treatment with these products fails despite their correct use, and reinfestation does not seem to be responsible, other topical treatment options include malathion, benzyl alcohol, dimethicone, spinosad and ivermectin. Wet combing should be considered for children younger than 2 years. Oral ivermectin and trimethoprim/sulfamethoxazole should be reserved for patients who do not respond to appropriate topical pediculicides.
CONCLUSION
Many topical pediculicides are effective for the treatment of pediculosis capitis. The use of some of these pediculicides is limited for safety reasons, especially in children younger than 2 years. Resistance to pediculicides, especially those with a neurotoxic mode of action, is another concern which may limit the use of some of these pediculicides. New products should be evaluated for effectiveness and safety. Wet combing is time-consuming and should not be used as the sole intervention in the general population.
PubMed: 35371269
DOI: 10.7573/dic.2021-11-3 -
Journal of Medical Entomology Mar 2022Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito...
Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito resistance after pre-exposure to PBO and subsequent enzymatic activity when exposed to PBO-synergized insecticides. We used Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of arboviruses and lymphatic filariasis, as a model to examine the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions pre- and post-PBO exposure. Mosquito eggs and larvae were collected from three cities in Orange County in July 2020 and reared in insectary, and F0 adults were used in this study. A JHB susceptible strain was used as a control. Mosquito mortalities and metabolic enzyme expressions were examined in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. Except for malathion, wild strain Cx quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality range 3.7 ± 4.7% to 66.7 ± 7.7%). Wild strain mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When wild strain mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compared to 0.02% for a susceptible strain. The knockdown resistance gene mutation (L1014F) rate was 62% in wild strain mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34% and GST by 11%, but had no impact on COE enzyme expression. Even with an optimal PBO concentration (7%) and exposure duration (3h), wild strain mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to the susceptible laboratory strain. These results further demonstrate other studies that PBO alone may not be enough to control highly pyrethroid-resistant mosquitoes due to multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored through a routine resistance management program for effective control of mosquitoes and the pathogens they transmit.
Topics: Animals; Culicidae; Cytochrome P-450 Enzyme System; Insecticide Resistance; Insecticides; Mosquito Control; Mosquito Vectors; Piperonyl Butoxide; Pyrethrins
PubMed: 35050361
DOI: 10.1093/jme/tjab231 -
Reproductive Toxicology (Elmsford, N.Y.) Sep 2022Piperonyl butoxide (PBO) was developed in the 1940s. PBO increases the effectiveness of pyrethrins, thus it is called a synergist. Herein, the findings from a guideline...
Piperonyl butoxide (PBO) was developed in the 1940s. PBO increases the effectiveness of pyrethrins, thus it is called a synergist. Herein, the findings from a guideline developmental toxicity study in rabbits conducted in 1986 are reported. Inseminated New Zealand White rabbits were randomly assigned to a control and three treatment groups of 16 does each. Dose levels of 50, 100 and 200 mg/kg/day were selected based on a dosage-range study to avoid excessive maternal toxicity and administered orally (gavage) as a single daily dose on days 7-19 of gestation at a volume of 0.5 mL/kg. The control group received the vehicle only, Mazola® corn oil. Cesarean sections were performed on all surviving females on gestation day 29 and fetuses were evaluated. Survival for all study groups was 100%. Treatment-related maternotoxicity was manifested at the 100 and 200 mg/kg/day levels as decreased defecation and dose-related body weight losses during the treatment period (gestation days 7-13 and 7-19). The Cesarean section parameter values and fetal morphological observations of the treated groups did not differ significantly from the concurrent control group and were within the historical control range for this rabbit strain. No maternal or fetal adverse effects were seen at the 50 mg/kg/day dose level. Although maternal toxicity resulting from treatment was apparent at the 100 and 200 mg/kg/day dose levels, neither fetotoxicity nor teratogenicity were elicited in rabbits by piperonyl butoxide at dose levels as high as 200 mg/kg/day.
Topics: Animals; Cesarean Section; Female; Piperonyl Butoxide; Pregnancy; Pyrethrins; Rabbits; Reproduction
PubMed: 35931401
DOI: 10.1016/j.reprotox.2022.07.009 -
Current Research in Parasitology &... 2022Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however,...
LLIN evaluation in Uganda project (LLINEUP): The fabric integrity, chemical content and bioefficacy of long-lasting insecticidal nets treated with and without piperonyl butoxide across two years of operational use in Uganda.
Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however, their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Uganda's 2017-2018 LLIN distribution to compare the durability of LLINs with and without PBO. A total of 104 clusters (health sub-districts) were included with each receiving one of four LLIN products, two with pyrethroid + PBO (Olyset Plus and PermaNet 3.0) and two pyrethroid-only (Olyset Net and PermaNet 2.0). Nets were sampled at baseline, 12 and 25 months post-distribution to assess physical condition, chemical content, and bioefficacy. Physical condition was quantified using proportionate Hole Index and chemical content measured using high-performance liquid chromatography. Bioefficacy was assessed with three-minute World Health Organisation (WHO) Cone and Wireball assays using pyrethroid-resistant , with 1-h knockdown and 24-h mortality recorded. There was no difference in physical durability between LLIN products assessed ( = 0.644). The pyrethroid content of all products remained relatively stable across time-points but PBO content declined by 55% ( < 0.001) and 58% ( < 0.001) for Olyset Plus and PermaNet 3.0 respectively. Both PBO LLINs were highly effective against pyrethroid-resistant mosquitoes when new, knocking down all mosquitoes. However, bioefficacy declined over time with Olyset Plus knocking down 45.72% (95% CI: 22.84-68.62%, = 0.021) and Permanent 3.0 knocking down 78.57% (95% CI: 63.57-93.58%, < 0.001) after 25 months. Here we demonstrate that both Olyset Plus and PermaNet 3.0 are as durable as their pyrethroid-only equivalents and had superior bioefficacy against pyrethroid-resistant . However, the superiority of PBO-LLINs decreased with operational use, correlating with a reduction in total PBO content. This decline in bioefficacy after just two years is concerning and there is an urgent need to assess the durability of PBO LLINs in other settings.
PubMed: 35734077
DOI: 10.1016/j.crpvbd.2022.100092 -
Reproductive Toxicology (Elmsford, N.Y.) Oct 2022Piperonyl butoxide (PBO) an insecticide synergist was evaluated in a guideline multigenerational toxicity study in rats. F0 and F1 adult generations consisted of groups...
Developmental and reproduction toxicity of piperonyl butoxide part 3 two generation (two litter) reproduction study of piperonyl butoxide administered in the diet to CD ® (Sprague Dawley) rats.
Piperonyl butoxide (PBO) an insecticide synergist was evaluated in a guideline multigenerational toxicity study in rats. F0 and F1 adult generations consisted of groups of 26 male and 26 female CD (Sprague Dawley) rats that were exposed to PBO in the diet at concentrations of 0, 300, 1000 or 5000 ppm for 85 (F0) or 83 (F1) days prior to cohabitation and throughout two mating periods (F1a, F2a and F1b, F2b). Exposure to test diets continued through the mating, gestation, and lactation periods for the females. F2 generation pups were euthanized following weaning. There were no effects on survival, clinical observations, gross or histological findings, fertility, pup viability, lactation indices or sex ratio in adults or pups in any generation. All effects of PBO occurred in the 5000-ppm exposure group. These effects included reduced body weight gains for F0 and F1 males and females during pre-cohabitation resulting in reduced body weights during both gestation periods. Food consumption of the F1b group males was slightly or significantly less than control values from week 3 onward. F1a generation pup weights were reduced on days 4, 7, 14 and 21 postpartum. Pup weights in the F1 and F2 generations were significantly reduced on days 14 and 21 postpartum when diets were being consumed by pups. The no-observable-adverse-effect level (NOAEL) for general toxicity was 1000 ppm based on reductions in body weights (parental and offspring) at 5000 ppm; and the NOAEL for reproductive toxicity was 5000 ppm with no direct effects on reproduction.
Topics: Animals; Body Weight; Diet; Female; Insecticides; Male; Piperonyl Butoxide; Rats; Rats, Sprague-Dawley; Reproduction
PubMed: 35963517
DOI: 10.1016/j.reprotox.2022.08.007 -
Reproductive Toxicology (Elmsford, N.Y.) Sep 2022Developed as an insecticide synergist in the early 1940s, PBO increases the effectiveness of pyrethrins. Herein, the findings from a guideline developmental toxicity...
Developed as an insecticide synergist in the early 1940s, PBO increases the effectiveness of pyrethrins. Herein, the findings from a guideline developmental toxicity study in rat conducted in 1991 are reported. Timed-pregnant CD® (Sprague Dawley) rats were randomly assigned to a control and three treatment groups of 25 females each. A single daily dose of 200, 500 and 1000 mg/kg/day was administered orally (gavage) on days 6-15 of gestation. A vehicle group received deionized water. Cesarean sections were performed on all surviving females on gestation day 21 and fetuses were evaluated. All rats survived to GD 21 of gestation. Pregnancy rates in each group ranged from 88 % to 96 %. One dam in the 500 mg/kg/day dose had a single conceptus litter (one early resorption). Adverse clinical observations (urogenital wetness and staining) occurred in the 1000 mg/kg/day dose group. Maternal body weight decrease and food reductions occurred over the dosing period in the 500 and 1000 mg/kg/day groups. There were no treatment-related maternal necropsy findings. Terminal body weights and gravid uterine weights were comparable among the groups. Corrected body weight gain was decreased (>10 %) at 500 and 1000 mg/kg/day. Increased liver weights and relative liver weights were observed in the 1000 mg/kg/day dose group. There were no treatment-related effects on early resorptions, late resorptions, live fetuses per litter or sex ratio, or fetal weight per litter among the dose groups and no fetal malformations or variations attributed to PBO at any dose level.
Topics: Animals; Body Weight; Female; Fetal Weight; Fetus; Piperonyl Butoxide; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction
PubMed: 35926829
DOI: 10.1016/j.reprotox.2022.07.010 -
Toxins Jun 2023The presence of insecticides like pyrethrins and synthetic pyrethroids, combined with the synergist piperonyl butoxide, in animal feeds can pose a risk to both animal...
The presence of insecticides like pyrethrins and synthetic pyrethroids, combined with the synergist piperonyl butoxide, in animal feeds can pose a risk to both animal and human health by contaminating the food chain. In this study, a simple and fast method was developed for the simultaneous determination of these compounds in contaminated animal feeds using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation was carried out using a QuEChERS-based approach, and the method was validated with acceptable accuracy ranging from 84 to 115% and precision below 10%. The limit of detection (LOD) and limit of quantification (LOQ) were between 0.15 and 3 and 1 and 10 µg/kg, respectively. The method detected insecticide contaminations in various livestock and poultry feeds. Furthermore, the method was applied to a toxicology case, where it identified and quantified piperonyl butoxide and deltamethrin in the submitted horse feed sample. These results demonstrate that the method can be a valuable tool in animal health and food safety diagnostic applications, as well as veterinary toxicology investigations concerning pyrethrin-related feed contamination.
Topics: Humans; Animals; Horses; Pyrethrins; Piperonyl Butoxide; Chromatography, Liquid; Tandem Mass Spectrometry; Insecticides; Animal Feed
PubMed: 37368701
DOI: 10.3390/toxins15060401 -
Chemosphere Feb 2021Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts... (Review)
Review
Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts as a pesticide synergist by inhibiting insect cytochrome P450 enzymes and is often present at much higher concentrations than active insecticidal ingredients. PBO was recently discovered to also inhibit Sonic hedgehog (Shh) signaling, a key molecular pathway in embryonic development and in brain and face morphogenesis. Recent animal model studies have shown that in utero PBO exposure can cause overt craniofacial malformations or more subtle neurodevelopmental abnormalities. Related adverse developmental outcomes in humans are etiologically heterogeneous, and, while studies are limited, PBO exposure during pregnancy has been linked to neurodevelopmental deficits. Contextualized in PBO's newly recognized mechanism as a Shh signaling inhibitor, these findings support more rigorous examination of the developmental toxicity of PBO and its potential contribution to etiologically complex human birth defects. In this review, we highlight environmental sources of human PBO exposure and summarize existing animal studies examining the developmental impact of prenatal PBO exposure. Also presented are critical knowledge gaps in our understanding of PBO's pharmacokinetics and potential role in gene-environment and environment-environment interactions that should be addressed to better understand the human health impact of environmental PBO exposure.
Topics: Animals; Embryonic Development; Female; Hedgehog Proteins; Humans; Insecticides; Morphogenesis; Pesticides; Piperonyl Butoxide; Pregnancy
PubMed: 33007564
DOI: 10.1016/j.chemosphere.2020.128414 -
Malaria Journal Oct 2023After decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of piperonyl butoxide and pyrethroid-treated long-lasting insecticidal nets (LLINs) versus pyrethroid-only LLINs with and without indoor residual spray against malaria infection: third year results of a cluster, randomised controlled, two-by-two factorial design trial in Tanzania.
BACKGROUND
After decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled, coinciding with the rapid spread of pyrethroid resistance. In a previously reported study, nets treated with a pyrethroid and a synergist, piperonyl butoxide (PBO), demonstrated superior efficacy compared to standard pyrethroid LLINs (std-LLINs) against malaria. Evidence was used to support the public health recommendation of PBO-Pyrethroid-LLIN by the World Health Organization in 2018. This study looks at the third year of rollout of these nets in Muleba district, Tanzania to inform whether policy guidelines need to be updated.
METHODS
A four-group cluster randomized trial (CRT) using a two-by-two factorial design was carried out between January 2014 and December 2017. A total of 48 clusters, were randomized in a 1:1:1:1 ratio to the following treatment groups, each intervention being provided once in 2015: 1/std-LLIN; 2/PBO-pyrethroid LLIN; 3/std-LLIN + Indoor Residual Spraying (IRS) and 4/PBO-Pyrethroid-LLIN + IRS. During the third year follow-up, malaria infection prevalence in 80 children per cluster, aged 6 months to 14 years, was measured at 28- and 33-months post-intervention and analysed as intention-to-treat (ITT) and per protocol (PP). Mosquito collections were performed monthly in all clusters, using CDC light traps in 7 randomly selected houses per cluster.
RESULTS
At 28 and 33 months, study net usage among household participants was only 47% and 31%, respectively. In ITT analysis, after 28 months malaria infection prevalence among 7471 children was 80.9% in the two std-LLIN groups compared to 69.3% in the two PBO-Pyrethroid-LLIN (Odds Ratio: 0.45, 95% Confidence Interval: 0.21-0.95, p-value: 0.0364). After 33 months the effect was weaker in the ITT analysis (prevalence 59.6% versus 49.9%, OR: 0.60, 95%CI:0.32-1.13, p-value: 0.1131) but still evident in the PP analysis (57.2% versus 44.2%, OR: 0.34, 95%CI: 0.16-0.71, p-value: 0.0051). Mean number of Anopheles per night collected per house was similar between PBO-Pyrethroid-LLIN groups (5.48) and std-LLIN groups (5.24) during the third year.
CONCLUSIONS
Despite low usage of PBO- Pyrethroid LLIN, a small impact of those nets on malaria infection prevalence was still observed in the 3rd year with the most protection offered to children still using them. To maximize impact, it is essential that net re-distribution cycles are aligned with this LLIN lifespan to maintain maximum coverage.
TRIAL REGISTRATION
The trial was registered with ClinicalTrials.gov (registration number NCT02288637).
Topics: Animals; Child; Humans; Anopheles; Insecticide Resistance; Insecticide-Treated Bednets; Insecticides; Malaria; Mosquito Control; Piperonyl Butoxide; Pyrethrins; Tanzania; Infant; Child, Preschool; Adolescent
PubMed: 37789389
DOI: 10.1186/s12936-023-04727-8